OBJECTIVES: To report efficacy of BG-12 (dimethyl fumarate) in pre-specified patient subgroups stratified by age, gender, treatment history, prior relapses, Expanded Disability Status Score (EDSS), McDonald criteria, T2 lesion volume, and presence/absence of gadolinium-enhancing lesions at baseline in a pre-specified integrated analysis of DEFINE and CONFIRM. This analysis was designed to estimate–more precisely–the treatment effect of BG-12 versus placebo. METHODS: Eligible patients were aged 18–55 years with a diagnosis of relapsing-remitting multiple sclerosis (RRMS) (McDonald criteria) and an EDSS score of 0–5.0. Patients receiving BG-12 240 mg twice (BID) or three times daily (TID) or placebo were included in this analysis. Primary endpoints were proportion of patients relapsed (DEFINE) and annualized relapse rate (ARR) (CONFIRM) at 2 years. Secondary endpoints included number of new/enlarging T2 lesions and disability progression. The pre-specified integrated analysis was to be conducted only if baseline characteristics and treatment effects were consistent between the studies. RESULTS: The integrated intent-to-treat population comprised 2,301 patients while MRI evaluations were performed in a cohort of 1,046 patients. Baseline characteristics and treatment effects were generally similar across studies. Both BG-12 BID and TID reduced ARR versus placebo at 2 years by approximately 50%, risk of relapse, number of new/enlarging T2 lesions, and risk of disability progression at 2 years versus placebo across the subgroups. For example, ARR versus placebo at 2 years was reduced by 50% (BID; rate ratio 0.50 [95% confidence interval 0.40–0.64]) and 53% (TID; 0.47 [0.37–0.60]) in patients with ≤1 relapse in the year before study entry and 47% (BID; 0.53 [0.40–0.72]) and 41% (TID; 0.59 [0.44–0.80]) in patients with ≥2 relapses. CONCLUSIONS: These findings further indicate consistent efficacy of BG-12 on both clinical and neuroradiological measures across a wide spectrum of RRMS patients.